The primary aim of this project is to define the specificity of interactions between cells mediating immunity to a syngeneic methylcholanthrene-induced fibrosarcoma, S1509a (H-2a). A source of soluble S1509a tumor antigen has been defined for use in the production of tumor-specific T-cell clones and the characterization of relevant antigens. T cells derived from S1509a-hyperimmune A/J (H-2a) hosts proliferate in vitro in response to soluble protein antigens present in S1509a ascites fluid. The response is directed predominantly to a 75 to 85 kilodalton molecule with a buoyant density of 1.2-1.32 gm/cc CsCl, with lesser recognition of certain low molecular weight components. Proliferation is specific in that no response is observed with similar preparations of YAC (H-2a) tumor antigens but exhibits cross-reactivity with the SA1 (H-2a) fibrosarcoma in keeping with the cross-protection that occurs in vivo. Tumor-specific suppressor T cells (Ts) do not appear to bind to the crude antigen preparation, supporting previous in vivo observations on the differential specificity of suppressor and effector T cells for S1509a and SA1 tumor-associated antigens. A second ongoing project involves the administration of monoclonal anti-I-A/I-E antibodies as a therapeutic approach to prolonging allogeneic transplant survival. We have found that the intravenous injection of 200 micrograms antibody/day for 10 days results in a 2-\to 3-fold enhancement in the survival of multiple minor or class I major histoin-compatible orthotopic tail grafts. Treatment is associated with the delayed development of donor-specific DTH and CTL reactivity concomitant with the appearance of alloantigen-specific Ts. Failure to alter the survival of H-2 incompatible grafts appears to be due to the differential recognition of class II versus class I H-2 or minor alloantigens by host Ts (manuscript in press). This therapy may prove beneficial in class II-matched kidney transplants, since treatment can be discontinued once suppression has been established, leaving the host response to subsequent antigenic challenges intact. (LB)